Several studies of the marine sedimentary record have documented the evolution of global climate during the Permo-Triassic mass extinction. By contrast, the continental records have been less exploited due to the scarcity of continuous sections from the latest Permian into the Early Triassic. The South African Karoo Basin exposes one of the most continuous geological successions of this time interval, thus offering the possibility to reconstruct climate variations in southern Laurasia from the Middle Permian to Middle Triassic interval. Both air temperature and humidity variations were estimated using stable oxygen (δ18Op) and carbon (δ13Cc) isotope compositions of vertebrate apatite. Significant fluctuations in both δ18Op and δ13Cc values mimic those of marine records and suggest that stable isotope compositions recorded in vertebrate apatite reflect global climate evolution. In terms of air temperature, oxygen isotopes show an abrupt increase of about + 8 °C toward the end of the Wuchiapingian. This occurred during a slight cooling trend from the Capitanian to the Permo-Triassic boundary (PTB). At the end of the Permian, an intense and fast warming of + 16 °C occurred and kept increasing during the Olenekian. These thermal fluctuations may be related to the Emeishan (South China) and Siberian volcanic paroxysms that took place at the end of the Capitanian and at the end of the Permian, respectively. Vertebrate apatite δ13Cc partly reflects the important fluctuations of the atmospheric δ13C values, the differences with marine curves being likely due to the evolution of local humidity. Both the oxygen and carbon isotope compositions indicate that the PTB was followed by a warm and arid phase that lasted 6 Ma before temperatures decreased, during the Late Anisian, toward that of the end-Permian. Environmental fluctuations occurring around the PTB that affected both continental and marine realms with similar magnitude likely originated from volcanism and methane release.